Radiographic signs of acetabular retroversion using a low-dose slot-scanning radiographic system (EOS^®)

Introduction: Acetabular retroversion is assessed using pelvic X-ray. Cross-over-sign (COS), posterior-wall-sign (PWS) and ischial-spine-sign (ISS) are important radiographic signs of the condition. The pelvic area is sensitive to radiation and thus, possibilities to reduce dose should be considered. The purpose was to compare radiographic signs of acetabular retroversion on conventional pelvic anteroposterior (AP) X-rays with a low-dose slot-scanning system (EOS) in a sample of patients with retroversion of the acetabulum and to compare the radiation doses. Methods: 34 participants with radiographic signs of acetabular retroversion in one or both hips on conventional pelvic X-ray were consecutively recruited. Pelvic EOS-images were acquired in each patient and COS, PWS, ISS, COS-ratio and PWS-ratio was assessed. Radiation dose comparison of X-ray vs. EOS was performed using Dose-Area Products. Results: Retroversion was present in 57 out of 68 hips. The absolute agreement was 91%, 84% and 76% for COS, PWS and ISS, respectively. No statistically significant differences were present between COS-ratio and PWS-ratio in either modality and Bland–Altman limits of agreement were narrow. The mean radiation dose was 1053 mGy*cm2 in X-ray and 593 mGy*cm2 in EOS (p = 0.003). Conclusion: The results indicate that pelvic EOS provides diagnostic qualities similar to conventional X-ray using 44% less radiation when radiographic signs of acetabular retroversion are assessed

Inherited crustal deformation along the East Gondwana margin revealed by seismic anisotropy tomography

Acknowledgments We thank Mallory Young for providing phase velocity measurements in mainland Australia and Tasmania. Robert Musgrave is thanked for making available his tilt-filtered magnetic intensity map. In the short term, data may be made available by contacting the authors (S.P. or N.R.). A new database of passive seismic data recorded in Australia is planned as part of a national geophysics data facility for easy access download. Details on the status of this database may be obtained from the authors (S.P., N.R., or A.M.R.). There are no restrictions on access for noncommercial use. Commercial users should seek written permission from the authors (S.P. or N.R.). Ross Cayley publishes with the permission of the Director of the Geological Survey of Victoria.Peer reviewedPublisher PD

Population pharmacokinetics of a new long-acting recombinant coagulation factor IX albumin fusion protein for patients with severe hemophilia B

Essentials The new recombinant factor IX (FIX) albumin fusion protein (rIX-FP) has a prolonged half-life. A population pharmacokinetic (PK) model was based on FIX activity levels of hemophilia B patients. The model was used to simulate different dosing scenarios of rIX-FP to help guide dosing. The population PK model supported prolonged dosing of rIX-FP with intervals of up to 2 weeks. Click to hear Prof.Makris's presentation on new treatments in hemophilia SUMMARY: Background The recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP; Idelvion® ) exhibits a longer half-life than plasma-derived factor IX (FIX) and the commercially available recombinant FIX products. Objectives (i) Characterize the population pharmacokinetics (PK) of rIX-FP in hemophilia B patients, (ii) identify covariates that are potential determinants of rIX-FP PK variability and (iii) simulate different dosing scenarios of rIX-FP following single and steady-state dosing. Patients/Methods A population PK model was developed based on FIX activity levels of 104 patients who had received treatment with rIX-FP. Patients were aged 1-65 years with FIX activity ≤ 2 IU dL-1 . PK sampling was performed for up to 14 days (336 h). Results Simulation of a single intravenous infusion of rIX-FP (25-75 IU kg-1 ) predicted that the median trough exogenous FIX activity levels would remain > 5 IU dL-1 for up to 16 days in adolescents/adults aged ≥ 12 years, up to 12 days in children aged 6 to 5 IU dL-1 for the duration of the dosing interval for the 25, 35 and 40 IU kg-1 weekly regimens and for 75 IU kg-1 every 14 days in adolescents/adults, and for the 35 and 40 IU kg-1 weekly regimens in children. Conclusion The population PK model developed here correlates well with observed clinical data and supports prolonged dosing of rIX-FP with intervals of up to 2 weeks

Evaluation of Patient-Reported Delays and Affordability-Related Barriers to Care in Head and Neck Cancer

Objective: To examine the prevalence and predictors of patient-reported barriers to care among survivors of head and neck squamous cell carcinoma and the association with health-related quality of life (HRQOL) outcomes. Study Design: Retrospective cohort study. Setting: Outpatient oncology clinic at an academic tertiary care center. Methods: Data were obtained from the UNC Health Registry/Cancer Survivorship Cohort. Barriers to care included self-reported delays in care and inability to obtain needed care due to cost. HRQOL was measured with validated questionnaires: general (PROMIS) and cancer specific (FACT-GP). Results: The sample included 202 patients with head and neck squamous cell carcinoma with a mean age of 59.6 years (SD, 10.0). Eighty-two percent were male and 87% were White. Sixty-two patients (31%) reported at least 1 barrier to care. Significant predictors of a barrier to care in unadjusted analysis included age ≤60 years (P =.007), female sex (P =.020), being unmarried (P =.016), being uninsured (P =.047), and Medicaid insurance (P =.022). Patients reporting barriers to care had significantly worse physical and mental HRQOL on the PROMIS questionnaires (P <.001 and P =.002, respectively) and lower cancer-specific HRQOL on the FACT-GP questionnaire (P <.001), which persisted across physical, social, emotional, and functional domains. There was no difference in 5-year OS (75.3% vs 84.1%, P =.177) or 5-year CSS (81.6% vs 85.4%, P =.542) in patients with and without barriers to care. Conclusion: Delay- and affordability-related barriers are common among survivors of head and neck cancer and appear to be associated with significantly worse HRQOL outcomes. Certain sociodemographic groups appear to be more at risk of patient-reported barriers to care

Association of self-reported financial burden with quality of life and oncologic outcomes in head and neck cancer

Background: There is a paucity of data on financial toxicity among patients with head and neck squamous cell carcinoma (HNSCC). Materials: This was a retrospective, cross-sectional study of patients with HNSCC surveyed at an outpatient oncology clinic. Results: The sample included 202 patients with HNSCC with a mean age of 59.6 years (SD 10.0). There were 53 patients (26%) with self-reported financial burden. Education of high school or less was a significant predictor of self-reported financial burden (OR 2.52, 95% CI 1.03–6.14, p = 0.042). Patients reporting financial burden had significantly worse physical (p = 0.003), mental (p = 0.003), and functional (p = 0.036) health-related quality of life (HRQOL). Patients reporting financial burden appeared to have lower 5-year overall survival (74.3% vs. 83.9%, p = 0.165), but this association did not reach statistical significance. Conclusion: Financial burden or toxicity may affect approximately a quarter of patients with HNSCC and appears to be associated with worse HRQOL outcomes

Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model

PURPOSE: The reoperation rate for breast-conserving surgery is as high as 15-30% due to residual tumor in the surgical cavity after surgery. In vivo tumor-targeted optical molecular imaging may serve as a red-flag technique to improve intraoperative surgical margin assessment and to reduce reoperation rates. Cysteine cathepsins are overexpressed in most solid tumor types, including breast cancer. We developed a cathepsin-targeted, quenched fluorescent activity-based probe, VGT-309, and evaluated whether it could be used for tumor detection and image-guided surgery in syngeneic tumor-bearing mice. METHODS: Binding specificity of the developed probe was evaluated in vitro. Next, fluorescent imaging in BALB/c mice bearing a murine breast tumor was performed at different time points after VGT-309 administration. Biodistribution of VGT-309 after 24 h in tumor-bearing mice was compared to control mice. Image-guided surgery was performed at multiple time points tumors with different clinical fluorescent camera systems and followed by ex vivo analysis. RESULTS: The probe was specifically activated by cathepsins X, B/L, and S. Fluorescent imaging revealed an increased tumor-to-background contrast over time up to 15.1 24 h post probe injection. In addition, VGT-309 delineated tumor tissue during image-guided surgery with different optical fluorescent imaging camera systems. CONCLUSION: These results indicate that optical fluorescent molecular imaging using the cathepsin-targeted probe, VGT-309, may improve intraoperative tumor detection, which could translate to more complete tumor resection when coupled with commercially available surgical tools and techniques

Modelling attrition and nonparticipation in a longitudinal study of prostate cancer

Abstract Background Attrition occurs when a participant fails to respond to one or more study waves. The accumulation of attrition over several waves can lower the sample size and power and create a final sample that could differ in characteristics than those who drop out. The main reason to conduct a longitudinal study is to analyze repeated measures; research subjects who drop out cannot be replaced easily. Our group recently investigated factors affecting nonparticipation (refusal) in the first wave of a population-based study of prostate cancer. In this study we assess factors affecting attrition in the second wave of the same study. We compare factors affecting nonparticipation in the second wave to the ones affecting nonparticipation in the first wave. Methods Information available on participants in the first wave was used to model attrition. Different sources of attrition were investigated separately. The overall and race-stratified factors affecting attrition were assessed. Kaplan-Meier survival curve estimates were calculated to assess the impact of follow-up time on participation. Results High cancer aggressiveness was the main predictor of attrition due to death or frailty. Higher Charlson Comorbidity Index increased the odds of attrition due to death or frailty only in African Americans (AAs). Young age at diagnosis for AAs and low income for European Americans (EAs) were predictors for attrition due to lost to follow-up. High cancer aggressiveness for AAs, low income for EAs, and lower patient provider communication scores for EAs were predictors for attrition due to refusal. These predictors of nonparticipation were not the same as those in wave 1. For short follow-up time, the participation probability of EAs was higher than that of AAs. Conclusions Predictors of attrition can vary depending on the attrition source. Examining overall attrition (combining all sources of attrition under one category) instead of distinguishing among its different sources should be avoided. The factors affecting attrition in one wave can be different in a later wave and should be studied separately

A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 20q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcript map of this interval using two parallel, complementary strategies to construct the map. We assembled a series of bacterial artificial chromosome (BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a greedy path searching algorithm, supplemented with local heuristics. We anchored the resulting BAC contigs and oriented them within a yeast artificial chromosome (YAC) scaffold by observing the retention patterns of shared markers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-based map from genomic sequence data released by the Human Genome Project, using a seed-and-walk approach. The map currently provides near-continuous coverage between SGC32867 and WI-17676 (∼ 6.0 Mb). EST database searches and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters enabled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidate genes and novel ESTs within the transcript map framework. So far, however, we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region